CARCINOGENIC/TOXICOLOGIC EFECTS OF PHIP AND DIETARY FAT ON RAT MAMMARY GLAND

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To better understand the mechanisms involved in mammary gland cancer induction by the food-derived heterocyclic amine 2-amino-1-methyl-6- phenylimidazo[4,5-b]pyridine (PhIP) and the effect of dietary fat, studies are underway to assess the early alterations induced by PhIP and dietary fat in the rat mammary gland. Mammary gland epithelial cell proliferation, apoptosis, and glandular development are being studied in an in vivo rat model. Female Sprague-Dawley rats were administered a carcinogenic dose regimen of PhIP and placed on either a high fat or low fat diet. At various times after carcinogen administration, mammary glands from rats were examined for premalignant histological alterations. Epithelial cell proliferation and apoptosis were examined by immunohistochemical methods. Mammary whole mounts were used to examine the effect of carcinogen and diet on the development of the gland. The preliminary results indicate that PhIP and dietary fat alter the rate of proliferation in the terminal end bud structures of the mammary gland.